Facility Upgrade Master Validation Plan

A facility upgrade master validation plan sets guidelines for modifications, additions and reconstruction so the facility can be validated and meets Environmental Room requirements. Installation Qualification and Operation Qualification are carried out on upgraded elements. Positive pressure is ≥ 0.05 in. water and temperature is 15 – 30°C, each monitored for a minimum of 72 hours.

1.1 PURPOSE: A facility upgrade master validation plan is a document that gives general guidelines for modifications, additions and reconstruction. These guidelines make validation of the facility possible. In addition to satisfying building codes, upgrades must satisfy Environmental Room requirements.

1.2 SCOPE: Installation Qualification (IQ) and Operation Qualification (OQ) will be conducted in the Environmental Room on upgraded elements. According to EU GMP Annex 15 and WHO GMP guidance on qualification and validation, IQ and OQ are qualification stages. For the difference between these terms, read validation, calibration and qualification in pharma.

REFERENCES This section lists the references for this plan. For related site documents, see the Index for Site Master File (SMF).

3.1. None

GLOSSARY This section defines the terms used in this plan.

4.1. Red-Line: The process of marking additions and changes on existing documents, drawings, and schematics with a red ink pen. Staff must sign and initial each modification. Staff must also document their printed name, initials, signature and date.

4.2. Tagging: The identification process where a physical item(s) is/are marked in such a way that a layperson can identify that item and track it to related documents.

4.3. Pests: Pests are invading biological entities.

4.4. Short Circuit: Producing a power draw where the current needed exceeds the rating of the circuit, resulting in a blown fuse.

4.5. Dead Air pocket: An area where air remains stagnant.

4.6. Activity: A situation where people and/or machines are moving within a room.

UPGRADE ELEMENTS: The facility upgrade master validation plan covers electrical, plumbing, facility (ceiling, walls, floors), HVAC and miscellaneous elements.

5.1. Electrical

5.2. Plumbing

5.3. Facility

5.3.1. Ceiling

5.3.2. Walls

5.3.3. Floors

5.4. HVAC / AC / Air Handlers

5.4.1. Ducts

5.4.2. Climate Control / Air Systems Units

5.5. Miscellaneous

5.5.1. Bug mitigation and elemental control

5.5.2. Pest extermination plan

5.5.3. Control systems, audible and displayed

REQUIREMENTS: This section gives the requirements of the facility upgrade master validation plan for IQ, OQ, Performance Qualification and post validation monitoring.

6.1. Installation Qualification6.1.1. Documentation

6.1.1.1. Modifications to existing schematics will be red-lined on all appropriate schematics, drawings, drafts, and any related documents.

6.1.1.2. The gage (wire thickness) of electrical wiring is identified, documented, and tagged.

6.1.1.3. Contractors providing services will provide a copy of their certification and qualifications for the tasks involved.

6.1.1.3.1. The contractors will be approved by Quality Assurance before the start of work.

6.1.1.4. A maximum power rating will be displayed either on the outlet or in any visible manner.

6.1.1.5. Fuses will be identified (with the location specified on fuse box listing) and rated properly for the circuit.

6.1.2. Facility

6.1.2.1. For All Items being installed in the Environmental Room or distally but relating to the room, the following must be provided, as appropriate:

6.1.2.1.1. Material Safety Data Sheets (MSDS) (where applicable), Purchase Orders, Purchase Requisitions, Drawings, Sketches, Schematics, Parts Lists, Packing Slips, Work Description or Plans, Manuals, Item Descriptions, Invoices, and any documentation that will identify items going into the upgrade process.

6.1.2.2. Walls

6.1.2.2.1. Paint used for walls will be identified and will be of a low or non-particulate emitting type and electro-static reducing.

6.1.2.3. Ceiling

6.1.2.3.1. Ceiling tiles will be sealed so that they will be low or non-particulate emitting.

6.1.2.4. Floors

6.1.2.4.1. Floors will be sealed with an appropriate sealant so that they will be low or non-particulate emitting.

6.1.2.4.2. Seams in the floor will be sealed so that no particles can be trapped.

6.1.2.4.3. The floor will be easy to sanitize.

6.1.2.4.4. Floor will be resistant to corrosives (i.e. sodium hydroxide and hydrochloric acid) and common solvents (i.e. ethanol and acetone).

6.1.2.4.5. The floor will be inert and will not react with chemicals.

6.1.2.4.6. Tacky mat stations will be installed at all entrances to the environmental room.

6.1.2.5. Miscellaneous

6.1.2.5.1. Barriers will be in place to prevent water and pests from entering the facility, including the warehouse.

6.1.2.5.2. Bug electrocuting units will be placed within 6 feet of all entrances to the environmental room facility.

6.1.2.5.2.1. At least one unit will be placed at each entrance.

6.1.2.5.2.2. The entrance to the warehouse will have at least 2 units.

6.1.2.5.3. An annual pest extermination inspection will be established.

6.1.2.5.3.1. The exterminator will be approved by Quality Assurance before the start of work.

6.1.2.5.3.2. Materials used for extermination will be identified and MSDSs provided, where applicable.

6.1.2.5.3.3. A post extermination inspection and documentation will be required.

6.1.3. HVAC / AC / Air Systems

For air handler performance checks, see the AHU Performance Qualification (PQ) Protocol.

6.1.3.1. HVAC and/or Air Handler Systems will be identified and the following information will be provided:

6.1.3.1.1. Descriptive: Model Number, Serial Numbers, Preventive Maintenance Procedures / Manuals, User’s Procedures / Manuals, Voltage requirement, Current requirement, Power rating, Phase and Frequency requirement, Drawings, Parts lists and Service providers.

6.1.3.1.2. Services and replacement parts will be identified.

6.1.3.1.3. A preventive maintenance plan will be identified and documented.

6.1.3.1.4. All air ducts will be identified from the air handler.

6.1.3.1.5. Average, Maximum, and Minimum air changes will be documented.

6.1.3.1.6. Filter suppliers will be identified.

6.1.3.1.7. A filter maintenance schedule will be developed.

6.1.3.2. Alarm systems will be installed for monitoring of positive air pressure, set to trigger at 0.05-in. water.

6.1.3.3. There will be dampers that will not allow negative pressure to exist within the environmental room.

6.2. Operation Qualification

6.2.1. Electrical

6.2.1.1. The voltage fluctuation on any circuit is +5 / -10 % of the total at any time with the electrical circuit being fully loaded.

6.2.1.2. The current drop on any circuit is ≤ 2% of the total at any time with the electrical circuit being fully loaded.

6.2.1.3. There will be no occurrence of a short circuit, with the circuit being loaded below the maximum threshold.

6.2.1.4. There will be a short circuit, with the circuit being loaded above the maximum threshold.

6.2.1.5. All electrical conduits will be sealed.

6.2.2. Ambient Air

6.2.2.1. Positive Pressure is ≥ 0.05 in. water.

6.2.2.1.1. The negative air created at the fume hood in the Quality Assurance (QA) room will not cause the QA or manufacturing room ambient air to fall below 0.05 in. of water.

6.2.2.1.2. The positive pressure will be monitored for a minimum of 72 hours.

6.2.2.1.3. The positive pressure alarm will be activated by forcing the room air to fall below 0.05 in. of water.

6.2.2.2. Temperature Control is controllable and will be maintained at 15 – 30°C.

6.2.2.2.1. The temperature will be monitored for a minimum of 72 hours.

6.2.2.3. Air changes are as determined by the minimum load possible of all the air handlers.

6.2.2.4. Air currents will be identified and documented using smoke studies.

6.2.2.4.1. No dead air pockets will exist.

6.2.2.5. The Particulate Matter (PM) reading will not exceed 91,000 pp cf/minute (parts per cubic foot per minute) at 0.5 microns and will not exceed 700 pp cf/minute at 5.0 micron.

6.2.2.5.1. During activity, PM readings will take place at 4 random positions each time within each room, at 0 (zero) hour and hour 2, two (2) times daily, for three (3) days.

6.2.2.6. The negative air pressure created at the fume hood in the Quality Assurance (QA) room will not cause the QA or manufacturing room ambient air to fall below 0.05 in. of water.

6.3. Performance Qualification

6.3.1. Performance Qualification (PQ) is not required because no input variables are associated that could affect the outcome of the finished product.

6.4. Post Validation Monitoring

6.4.1. A plan will be developed for routine monitoring of ambient particulate matter.

6.4.1.1. The interval of monitoring will be established based on preliminary results.

6.4.2. A per biennium smoke study will be performed to verify the absence of dead air pockets.

6.4.3. Positive air pressure alarm will be tested quarterly.

Frequently Asked Questions

What is the scope of the plan?

The plan’s scope is Installation Qualification and Operation Qualification. Both are conducted in the Environmental Room on upgraded elements. Upgrades must also satisfy building codes and Environmental Room requirements. The plan gives general guidelines for modifications, additions and reconstruction so that the facility can be validated.

Is Performance Qualification required?

Performance Qualification (PQ) is not required. No input variables are associated that could affect the outcome of the finished product. The plan therefore covers only Installation Qualification and Operation Qualification, which are carried out in the Environmental Room on upgraded elements.

What are the upgrade elements?

The plan lists five upgrade elements: electrical, plumbing, facility, HVAC / AC / Air Handlers, and miscellaneous. Facility covers the ceiling, walls and floors. HVAC covers ducts and climate control or air systems units. Miscellaneous covers bug mitigation and elemental control, a pest extermination plan, and audible and displayed control systems.

What are the main air acceptance criteria?

Positive pressure must be ≥ 0.05 in. water and is monitored for a minimum of 72 hours. Temperature is maintained at 15 – 30°C and is also monitored for a minimum of 72 hours. The positive pressure alarm is set to trigger at 0.05-in. water.

What are the particulate matter limits?

The Particulate Matter (PM) reading will not exceed 91,000 pp cf/minute (parts per cubic foot per minute) at 0.5 microns. It will not exceed 700 pp cf/minute at 5.0 micron. During activity, readings are taken at 4 random positions each time within each room, at 0 (zero) hour and hour 2, two (2) times daily, for three (3) days.

What post validation monitoring is required?

After validation, particulate matter is monitored routinely, a smoke study is repeated per biennium, and the positive air pressure alarm is tested quarterly. The interval of particulate monitoring will be established based on preliminary results. The smoke study verifies the absence of dead air pockets.

What must contractors provide?

Contractors providing services must provide a copy of their certification and qualifications for the tasks involved. Quality Assurance must approve the contractors before the start of work. The exterminator also needs Quality Assurance approval before the start of work.